Calcitriol and Hypercalcemia in Non-Hodgkin Lymphoma (NHL)

Introduction: Hypercalcemia is most commonly attributed to dehydration and treated with intravenous fluids. However, it is often associated with malignancies and in rare cases such as ours, it can be the first clinical presentation of an underlying malignancy and the only clinical finding for years. Case Description: An 83-year-old female had multiple admissions over 3 years with persistent hypercalcemia, discovered after a fall. Work-up showed IgM Kappa M spike, and bone marrow biopsy ruled out multiple myeloma. Despite weekly IV hydration, she had recurrent admissions with hypercalcemia (13-15 mg/dl) and acute kidney injury (AKI) with peak creatinine of 2.5 mg/dl. Renal work-up showed bland urine sediment and normal imaging.She declined bisphosphonate or denosumab therapy, and hypercalcemia and AKI would partially improve with IV hydration, and then subsequently worsen on follow-up On readmission, calcium was 13.3 mg/dl. Work-up showed suppressed intact parathyroid hormone (iPTH) levels of 12 pg/mL, PTH-related protein levels normal at 10 pmol/L, elevated 1,25 vitamin D (98 pg/mL), and low-normal 25 vitamin D (32 ng/mL). PET scan revealed lymph nodes with increased metabolic activity. Left cervical node biopsy showed B-cell NHL and as per the final report, on the basis of clinical, histologic, immunophenotypic, and genetic findings, the differential diagnosis would include nodal marginal zone lymphoma with follicular colonization, and classic follicular lymphoma (WHO 5) with marginal zone and plasmacytic differentiation She received prednisone taper and Rituximab infusions. Calcium normalized at 9-month follow-up. Renal function stabilized at CKD stage 3b, and she no longer needs IV hydration. Discussion: Multiple mechanisms cause hypercalcemia in NHL, including PTHrP, or osteolytic metastases. Our case was increased calcitriol from extra-renal 1-alpha-hydroxylase activity by NHL cells. Calcitriol increases serum calcium through gastrointestinal absorption and renal reabsorption, causing hypercalcemia in one-third of NHL cases. Hypercalcemia indicates poor prognosis in NHL, particularly with low PTH levels. Treatment involves addressing lymphoma. Persistent hypercalcemia without obvious causes can indicate underlying malignancy, affecting both AKI and CKD. Bisphosphonates can affect renal function, and denosumab has insufficient evidence.